Background: Behçet’s disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications: no laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available in the clinical practice. Objectives: To search for a correlation between serum amyloid-A (SAA) levels and disease activity evaluated via BD current activity form (BDCAF), to assess disease activity in relationship with different SAA thresholds, to examine the association between single organ involvements and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels. Methods: Ninety-five serum samples were collected from 64 BD patients, and their related demographic, clinical and therapeutic data were retrospectively collected. Results: No correlation was identified between SAA levels and BD disease activity (Spearman rho=0.085; p=0.411), while a significant difference was found in the mean BDCAF score between patients presenting SAA levels <200 mg/l and those with SAA levels >200 mg/L (p=0.027). SAA levels higher than 200 mg/l were significantly associated with major organ involvement (p=0.008, Phi 0.294). A significant association was found between SAA levels >150 mg/dl and ocular (p=0.008, Phi 0.337), skin (p=0.002, Phi 0.351) and mucosal manifestations (p=0.012, Phi 0.349). Patients undergoing biologic therapies were significantly associated with SAA levels <200 mg/l compared with patients who were not treated with biologics (p=0.012 Phi -0,284). Conclusions: SAA level does not represent per se a biomarker of disease activity, but might be useful as a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD.